The Centers for Disease Control reports that Echinacea is the third most commonly used herbal medicine in the US. Echinacea is typically employed for treatment of upper respiratory infections, which afflict adults two-four times per year, and cost over $10 billion in annual medical costs. Several Echinacea preparations and constituents thereof have demonstrated the ability to suppress inflammation, and may, therefore, be indicated in treating the symptoms of upper respiratory infections. While Echinacea demonstrated promise for this purpose in some early trials, a number of recent clinical trials have shown certain Echinacea extracts to be ineffective for treatment of upper respiratory infections. These conflicting findings may be explained at least in part by several issues with the composition of the study materials used in Echinacea research. There is still a lack of knowledge as to which specific constituents of Echinacea are appropriate markers for anti-inflammatory effects. Furthermore, among the many constituents present in complex Echinacea extracts are several that can stimulate the immune response, an activity that is likely to be undesirable when treating the symptoms of upper respiratory infections. A further complicating factor is that these immunostimulatory constituents may be produced by endophytic bacteria, bacteria that live within the Echinacea purpurea plants. With the proposed research, we seek to demonstrate ideal constituent profiles for anti-inflammatory Echinacea purpurea preparations, and to demonstrate procedures to remove constituents that stimulate the immune response. Toward this goal, we will employ a method recently developed in our research laboratory, synergy-directed fractionation, which enables the presence of specific constituents in crude extracts to be linked to biological activity. This approach can be used to identify components of complex mixtures that interact synergistically, additively, or antagonistically. As an outcome of our studies, we expect to enable more effective quality control of Echinacea purpurea extracts used for scientific research or to treat upper respiratory infections. PUBLIC HEALTH RELEVANCE: This project is relative to public health because it involves investigation of the immensely popular botanical medicine Echinacea, which is used to treat upper respiratory infections such as colds and influenza. Influenza A infections are responsible for an estimated 30,000 deaths each year in the US. With the proposed research, we seek to provide insight into the production of Echinacea preparations with enhanced efficacy for treating infections such as these.